Dietary Supplementation of Genistein Attenuates Inflammatory Responses and Oxidative Stress during Cutaneous Wound Healing in Diabetic Mice

Delayed wound healing is one of the most serious diabetic complications. This is mainly due to increased impairment of inflammatory response and oxidative stress in diabetic tissues. In this study, we investigated whether genistein supplementation attenuated inflammatory response and oxidative stress during the early stage of cutaneous wound healing in alloxan-induced diabetic mice. Diabetes was induced by administration of alloxan monohydrate. Mice with diabetes [fasting blood glucose (FBG) levels >= 250 mg/dl] were fed AIN-93G rodent diet contained 0%, 0.025% or 0.1% genistein. Diabetic mice showed increased hepatic MDA concentration, delayed wound closure rate, and dysregulated hepatic antioxidant enzyme expression compared to nondiabetic mice. However, genistein supplementation decreased hepatic MDA levels, accelerated wound closure rate, and rectified hepatic antioxidant enzymes expression under diabetic condition without regulation of FBG levels. Moreover, diabetic mice had excessive inflammatory responses such as increases in NFkB, pIkB, TNFa, COX-2, and iNOS and dysregulation of the antioxidant defense system demonstrated by Nrf2, HO-1 and MnSOD during the inflammatory phase of cutaneous wound healing, contrary to nondiabetic mice. However, genistein supplementation accelerated wound closure rate by modulation of both inflammatory response and oxidative stress-related markers in diabetic mice. Taken together, we suggest that genistein would be a potential therapeutic in prevention and treatment of delayed wound healing in diabetic patients by regulation of inflammatory response and oxidative stress.